Ca2+-Triggered Synaptic Vesicle Fusion Initiated by Release of Inhibition

Axel T Brunger; Jeremy Leitz; Qiangjun Zhou; Ucheor B Choi; Ying Lai

doi:10.1016/j.tcb.2018.03.004

Ca²⁺-Triggered Synaptic Vesicle Fusion Initiated by Release of Inhibition

Trends Cell Biol. 2018 Aug;28(8):631-645. doi: 10.1016/j.tcb.2018.03.004. Epub 2018 Apr 26.

Authors

Axel T Brunger¹, Jeremy Leitz², Qiangjun Zhou², Ucheor B Choi², Ying Lai²

Affiliations

¹ Department of Molecular and Cellular Physiology, Stanford University, Stanford, CA, USA; Department of Neurology and Neurological Sciences, Stanford University, Stanford, CA, USA; Department of Structural Biology, Stanford University, Stanford, CA, USA; Department of Photon Science, Stanford University, Stanford, CA, USA; Howard Hughes Medical Institute, Stanford University, Stanford, CA, USA. Electronic address: brunger@stanford.edu.
² Department of Molecular and Cellular Physiology, Stanford University, Stanford, CA, USA; Department of Neurology and Neurological Sciences, Stanford University, Stanford, CA, USA; Department of Structural Biology, Stanford University, Stanford, CA, USA; Department of Photon Science, Stanford University, Stanford, CA, USA; Howard Hughes Medical Institute, Stanford University, Stanford, CA, USA.

Abstract

Recent structural and functional studies of the synaptic vesicle fusion machinery suggest an inhibited tripartite complex consisting of neuronal soluble N-ethylmaleimide sensitive factor attachment protein receptors (SNAREs), synaptotagmin, and complexin prior to Ca²⁺-triggered synaptic vesicle fusion. We speculate that Ca²⁺-triggered fusion commences with the release of inhibition by Ca²⁺ binding to synaptotagmin C2 domains. Subsequently, fusion is assisted by SNARE complex zippering and by active membrane remodeling properties of synaptotagmin. This additional, inhibitory role of synaptotagmin may be a general principle since other recent studies suggest that Ca²⁺ binding to extended synaptotagmin C2 domains enables lipid transport by releasing an inhibited state of the system, and that Munc13 may nominally be in an inhibited state, which is released upon Ca²⁺ binding to one of its C2 domains.

Keywords: Ca(2+) triggering; action potential; fusion protein; synaptic vesicle fusion; synaptic vesicle priming.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Review

MeSH terms

Animals
Binding Sites / drug effects
C2 Domains / drug effects
Calcium / metabolism
Calcium / pharmacology*
Humans
SNARE Proteins / antagonists & inhibitors
SNARE Proteins / metabolism
Synaptic Vesicles / drug effects*
Synaptic Vesicles / metabolism*
Synaptotagmin I / antagonists & inhibitors
Synaptotagmin I / metabolism

Substances

SNARE Proteins
Synaptotagmin I
Calcium

Abstract

Publication types

MeSH terms

Substances

Grants and funding